Potential regulatory roles for G protein-coupled receptor kinases and beta-arrestins in gonadotropin-releasing hormone receptor signaling
| Autor: | L W Duck, Lois C. Musgrove, Jeffrey C. Sellers, Jimmy D. Neill |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
endocrine system
medicine.medical_specialty Arrestins Inositol Phosphates Gonadotropin-releasing hormone Biology Transfection Gonadotropin-Releasing Hormone Endocrinology Thyrotropin-releasing hormone receptor GTP-Binding Proteins Pituitary Gland Anterior Internal medicine medicine Arrestin Animals 5-HT5A receptor Phosphorylation beta-Arrestins G protein-coupled receptor G protein-coupled receptor kinase Receptor Protein-Tyrosine Kinases Molecular biology Immunohistochemistry beta-Arrestin 2 Rats Kinetics beta-Arrestin 1 COS Cells Arrestin beta 2 Cattle hormones hormone substitutes and hormone antagonists Gonadotropin-releasing hormone receptor Receptors LHRH Signal Transduction |
| Zdroj: | Endocrinology. 139(4) |
| ISSN: | 0013-7227 |
| Popis: | GnRH stimulates gonadotropin secretion, which desensitizes unless the releasing hormone is secreted or administered in a pulsatile fashion. The mechanism of desensitization is unknown, but as the GnRH receptor is G protein coupled, it might involve G protein-coupled receptor kinases (GRKs). Such kinases phosphorylate the intracellular regions of seven-transmembrane receptors, permitting β-arrestin to bind, which prevents the receptor from activating G proteins. Here, we tested the effect of GRKs and β-arrestins on GnRH-induced inositol trisphosphate (IP3) production in COS cells transfected with the GnRH receptor complementary DNA. GRK2, -3, and -6 overexpression inhibited IP3 production by 50–75% during the 30 sec of GnRH treatment. Coexpression of GRK2 and β-arrestin-2 suppressed GnRH-induced IP3 production more than that of either alone. Immunocytochemical staining of rat anterior pituitary revealed that all cells expressed GRK2, -3, and -6; all cells also expressed theβ -arrestins. Western blots on cytosolic extracts of rat pituitaries revealed the presence of GRK2/3 and β-arrestin-1 and -2. The expression of GRKs and β-arrestins by gonadotropes and their inhibition of GnRH-stimulated IP3 production in COS-1 cells expressing the GnRH receptor suggest a potential regulatory role for the GRK/β arrestin paradigm in GnRH receptor signaling. |
| Databáze: | OpenAIRE |
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